Clarification of the mechanism of the cochlear nerve degeneration in an animal model of deafness

阐明耳聋动物模型中耳蜗神经变性的机制

• 批准号: 11671669
• 负责人: IKEDA Katsuhisa
• 金额: $ 1.34万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671669/
• 关键词: Deafness gene; Mutation; Brn; GJB2; Konckout mice; Gene transfer; Endocochlear potential; K recysling; Brain; 転写因子; 難聴; ABR; 内リンパ電位; 線維細胞; K^+イオン; Brn-3.1; ノックアウトマウス; 蝸牛神経; 内リンパ静止電位

DFN3, an X-linked nonsyndromic mixed deafness is caused by mutations in BRN gene, which encodes a POU transcription factor gene. By gene targeting technology Brn-deficient mice were created and found to exhibit profound deafness. No gross morphological changes were observed in the conductive ossicles or cochlea, although there was a drastic reduction in endocochlear potential (EP). Electron microscopy revealed severe ultrastructural alterations in cochlear spiral ligament fibrocytes. These findings suggest that these fibrocytes, which are mesenchymal in origin and have been postulated to function in K^+ homeostasis, may play a critical role in auditory function and show a major cause of the hereditary deafness.

DFN3 是一种 X 连锁非综合征性混合性耳聋，由编码 POU 转录因子基因的 BRN 基因突变引起。通过基因靶向技术，Brn 缺陷小鼠被培育出来，并被发现表现出严重的耳聋。尽管耳蜗内电位（EP）急剧下降，但传导听小骨或耳蜗没有观察到明显的形态变化。电子显微镜显示耳蜗螺旋韧带纤维细胞发生严重的超微结构改变。这些发现表明，这些纤维细胞起源于间充质，并被认为在 K^+ 稳态中发挥作用，可能在听觉功能中发挥关键作用，并显示出遗传性耳聋的主要原因。

项目成果

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Oshima 等人：“线粒体基因导致听力损失”喉镜。